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Updated: Sep 11, 2025

Cerebral Blood Flow-Based Resting State Functional Connectivity of the Human Brain using Optical Diffuse Correlation Spectroscopy
Published on: May 27, 2020
Macrovascular contributions to resting-state fMRI signals: A comparison between EPI and bSSFP at 9.4 Tesla
Dana Ramadan1, Sebastian Mueller1, Ruediger Stirnberg2
1High-Field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany.
Abstract:
The draining-vein bias of T2*-weighted sequences, like gradient echo echo-planar imaging (GRE-EPI), can limit the spatial specificity of functional MRI (fMRI). The underlying extravascular signal changes increase with field strength (B0) and the perpendicularity of draining veins to the main axis of B0, and are, therefore, particularly problematic at ultra-high field (UHF). In contrast, simulations showed that T2-weighted sequences are less affected by the draining-vein bias, depending on the amount of rephasing of extravascular signal. As large pial veins on the cortical surface follow the cortical folding tightly, their orientation can be approximated by the cortical orientation to . In our work, we compare the influence of the cortical orientation to on the resting-state fMRI signal of three sequences aiming to understand their macrovascular contribution. While 2D GRE-EPI and 3D GRE-EPI (both T2*-weighted) showed a high dependence on the cortical orientation to , especially on the cortical surface, this was not the case for 3D balanced steady-state free precession (bSSFP) (T2/T1-weighted). Here, a slight increase of orientation dependence was shown in depths closest to white matter (WM). And while orientation dependence decreased with increased distance to the veins for both EPI sequences, no change in orientation dependence was observed in bSSFP. This indicates the low macrovascular contribution to the bSSFP signal, making it a promising sequence for layer fMRI at UHF.
Insights
Gradient echo echo-planar imaging (GRE-EPI) fMRI sequences are limited by draining-vein bias at ultra-high fields. Balanced steady-state free precession (bSSFP) sequences show less macrovascular signal contribution, making them promising for layer fMRI.
Area of Science:
- Neuroimaging
- Magnetic Resonance Imaging (MRI)
- Functional MRI (fMRI)
Background:
- T2*-weighted sequences, such as gradient echo echo-planar imaging (GRE-EPI), suffer from draining-vein bias, limiting spatial specificity in functional MRI (fMRI).
- This bias is exacerbated at ultra-high fields (UHF) due to increased extravascular signal changes and vein orientation relative to the main magnetic field (B0).
- T2-weighted sequences are theoretically less susceptible to draining-vein bias, depending on extravascular signal rephasing.
Purpose of the Study:
- To compare the influence of cortical orientation relative to B0 on resting-state fMRI signals across three different imaging sequences.
- To understand and quantify the macrovascular contribution to the fMRI signal for each sequence at UHF.
- To evaluate the suitability of different sequences for layer-specific fMRI at UHF.
Main Methods:
- Comparison of 2D GRE-EPI (T2*-weighted), 3D GRE-EPI (T2*-weighted), and 3D balanced steady-state free precession (bSSFP) (T2/T1-weighted) sequences.
- Analysis of resting-state fMRI signal dependence on cortical vein orientation relative to the main magnetic field (B0).
- Assessment of orientation dependence at varying distances from cortical veins and in relation to white matter (WM) boundaries.
Main Results:
- Both 2D and 3D GRE-EPI sequences exhibited strong dependence on cortical orientation relative to B0, particularly on the cortical surface.
- 3D bSSFP showed minimal orientation dependence, with only a slight increase observed near the white matter boundary.
- Orientation dependence decreased with distance from veins for GRE-EPI sequences, whereas bSSFP demonstrated no change in orientation dependence, indicating a low macrovascular signal contribution.
Conclusions:
- 3D bSSFP sequences are less affected by draining-vein bias compared to GRE-EPI sequences at UHF.
- The minimal macrovascular contribution to the bSSFP signal makes it a promising candidate for high-resolution, layer-fMRI at UHF.
- Understanding sequence-specific biases is crucial for accurate interpretation of fMRI data, especially for layer-specific analyses at UHF.

